Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: towards the design of anticancer vaccines.
Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: towards the design of anticancer vaccines.
复制标题
路易斯（y）寡糖与蛋白质的合成缀合物在小鼠中的免疫原性：针对抗癌疫苗的设计。
DOI：
10.1007/s002620050444
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Lloyd,KO
中科院分区：
文献类型：
--
作者：
Kudryashov,V;Kim,HM;Ragupathi,G;Danishefsky,SJ;Livingston,PO;Lloyd,KO
许多人类肿瘤过表达Lewisy（Ley）血型表位[Fucα1→2Galβ1→4 (Fucα1→3)GlcNAcβ1→3Gal-]。为了研制Leybased疫苗，我们在小鼠中检测了ley蛋白偶联物的免疫原性。以烯丙基糖苷的形式合成了雷五糖，并通过还原胺化或利用马来烯基衍生物烷基羧基肼作为桥接基团与2-亚氨基硫烷衍生物KLH偶联到锁孔帽贝血青素（KLH）上。leyoligaccharide也通过还原性胺化作用与牛血清白蛋白偶联。用这三种偶联物和免疫佐剂QS21对小鼠进行免疫，结果表明，与KLH直接偶联的Leyoligosaccharide是最有效的偶联物，可诱导IgG和IgM抗体对天然存在的Leyepitopes粘蛋白和糖脂携带的抗体产生应答。这些抗体对表达Ley（MCF-7）的人乳腺癌细胞系也有反应性和细胞毒性。提示Ley-KLH抗原和QS21佐剂可作为肿瘤患者的免疫原性治疗疫苗。
Many human carcinomas overexpress the Lewisy(Ley) blood-group epitope [Fucα1→2Galβ1→4 (Fucα1→3)GlcNAcβ1→3Gal-]. With a view to developing Leybased vaccines we have examined the immunogenicity of Ley-protein conjugates in mice. Leypentasaccharide was synthesized as its allyl glycoside and coupled to keyhole limpet hemocyanin (KLH) by reductive amination or by a novel method utilizing a maleido-derivitized alkyl carboxyhydrazide as a bridging group to 2-iminothiolane-derivitized KLH. Leyoligosaccharide was also coupled to bovine serum albumin by reductive amination. Immunization of groups of mice with the three conjugates, together with the immunological adjuvant QS21, showed that Leyoligosaccharide directly coupled to KLH was the most efficient conjugate for eliciting IgG and IgM antibody responses to naturally occurring forms of Leyepitopes carried on mucins and glycolipids. These antibodies were also reactive with and cytotoxic to a human breast cancer cell line expressing Ley(MCF-7). These experiments suggest that Ley-KLH antigen and QS21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma patients.